Devanand D P, Goldberg Terry E, Qian Min, Rushia Sara N, Sneed Joel R, Andrews Howard F, Nino Izael, Phillips Julia, Pence Sierra T, Linares Alexandra R, Hellegers Caroline A, Michael Andrew M, Kerner Nancy A, Petrella Jeffrey R, Doraiswamy P Murali
Division of Geriatric Psychiatry, New York State Psychiatric Institute, New York.
Department of Psychiatry, Columbia University Medical Center, New York.
NEJM Evid. 2022 Dec;1(12). doi: 10.1056/evidoa2200121. Epub 2022 Oct 27.
Mild cognitive impairment (MCI) increases the risk of dementia. The efficacy of cognitive training in patients with MCI is unclear.
In a two-site, single-blinded, 78-week trial, participants with MCI - stratified by age, severity (early/late MCI), and site - were randomly assigned to 12 weeks of intensive, home-based, computerized training with Web-based cognitive games or Web-based crossword puzzles, followed by six booster sessions. In mixed-model analyses, the primary outcome was change from baseline in the 11-item Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) score, a 70 point scale in which higher scores indicate greater cognitive impairment at 78 weeks, adjusted for baseline. Secondary outcomes included change from baseline in neuropsychological composite score, University of California San Diego Performance-Based Skills Assessment (functional outcome) score, and Functional Activities Questionnaire (functional outcome) score at 78 weeks, adjusted for baseline. Changes in hippocampal volume and cortical thickness on magnetic resonance imaging were assessed.
Among 107 participants (n=51 [games]; n=56 [crosswords]), ADAS-Cog score worsened slightly for games and improved for crosswords at week 78 (least squares [LS] means difference, -1.44; 95% confidence interval [CI], -2.83 to -0.06; P=0.04). From baseline to week 78, mean ADAS-Cog score worsened for games (9.53 to 9.93) and improved for crosswords (9.59 to 8.61). The late MCI subgroup showed similar results (LS means difference, -2.45; SE, 0.89; 95% CI, -4.21 to -0.70). Among secondary outcomes, the Functional Activities Questionnaire score worsened more with games than with crosswords at week 78 (LS means difference, -1.08; 95% CI, -1.97 to -0.18). Other secondary outcomes showed no differences. Decreases in hippocampal volume and cortical thickness were greater for games than for crosswords (LS means difference, 34.07; SE, 17.12; 95% CI, 0.51 to 67.63 [hippocampal volume]; LS means difference, 0.02; SE, 0.01; 95% CI, 0.00 to 0.04 [cortical thickness]).
Home-based computerized training with crosswords demonstrated superior efficacy to games for the primary outcome of baseline-adjusted change in ADAS-Cog score over 78 weeks. (Supported by the National Institutes of Health, National Institute on Aging; ClinicalTrials.gov number, NCT03205709.).
轻度认知障碍(MCI)会增加患痴呆症的风险。认知训练对MCI患者的疗效尚不清楚。
在一项为期78周的双中心、单盲试验中,将MCI患者按年龄、严重程度(早期/晚期MCI)和中心进行分层,随机分配至接受为期12周的强化家庭式计算机训练,训练内容为基于网络的认知游戏或基于网络的填字游戏,随后进行6次强化训练。在混合模型分析中,主要结局是经基线校正后的11项阿尔茨海默病评估量表-认知部分(ADAS-Cog)评分在78周时相对于基线的变化,该量表满分为70分,分数越高表明认知障碍越严重。次要结局包括经基线校正后的78周时神经心理综合评分、加利福尼亚大学圣地亚哥分校基于表现的技能评估(功能结局)评分和功能活动问卷(功能结局)评分相对于基线的变化。评估了磁共振成像上海马体积和皮质厚度的变化。
在107名参与者中(游戏组n = 51;填字游戏组n = 56),78周时游戏组的ADAS-Cog评分略有恶化,而填字游戏组有所改善(最小二乘均值差异为-1.44;95%置信区间为-2.83至-0.06;P = 0.04)。从基线到78周,游戏组的平均ADAS-Cog评分恶化(从9.53变为9.93),而填字游戏组有所改善(从9.59变为8.61)。晚期MCI亚组显示出相似的结果(最小二乘均值差异为-2.45;标准误为0.89;95%置信区间为-4.21至-0.70)。在次要结局中,78周时功能活动问卷评分在游戏组中的恶化程度比填字游戏组更大(最小二乘均值差异为-1.08;95%置信区间为-1.97至-0.18)。其他次要结局无差异。游戏组海马体积和皮质厚度的减少幅度大于填字游戏组(最小二乘均值差异为34.07;标准误为17.12;95%置信区间为0.51至67.63[海马体积];最小二乘均值差异为0.02;标准误为0.01;95%置信区间为0.00至0.04[皮质厚度])。
在经基线校正的78周ADAS-Cog评分这一主要结局方面,基于家庭的填字游戏计算机训练显示出优于游戏训练的疗效。(由美国国立卫生研究院国家老龄研究所资助;ClinicalTrials.gov编号,NCT03205709。)